A Beginner s Guide to BRCA1 and BRCA2

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1 i A Beginner s Guide to BRCA1 and BRCA2

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3 A Beginner s Guide to BRCA1 and BRCA2 Contents Page Introduction What does it mean to have a BRCA gene mutation? 1 Background information about the BRCA1/2 genes 2 Screening Managing your risk of breast cancer 4 Managing your risk of ovarian cancer 8 Reducing risk Risk-reducing mastectomy 11 Risk-reducing ovarian surgery and surgical menopause 13 Sharing information with your family General issues 24 Who is at risk of having the faulty gene in my family? 26 Men and BRCA genes: What do men need to know? 29 Predictive genetic testing 31 A letter for your relatives 33 Passing on the cancer gene: How to tell the family 37 Talking to children and young people about BRCA 40 Adoption 45 Predictive genetic testing and insurance 46 Did you know? Family Planning 49 Pre-implantation Genetic Diagnosis 51 BRCA genes and the Ashkenazi Jewish population 53 Current studies and trials 54 New cancer treatment options for BRCA carriers 55 Organ donation 57 Where can I get more information? 59

4 Acknowledgements We would like to express our gratitude to Macmillan Cancer Support who provided funding for the pilot phase of this project. Macmillan Cancer Support improves the lives of people affected by cancer. They provide practical, medical, emotional and financial support and push for better cancer care.

5 A Beginner s Guide to BRCA1 and BRCA2 Introduction What does it mean to have a BRCA gene mutation? This information pack was put together to provide answers to some of the many questions people have when they receive the news that they are BRCA gene mutation carriers. Healthcare professionals working in Cancer Genetics have met many people who are BRCA carriers and we can share our experience to some extent. We can provide information and make referrals to other healthcare professionals. We can tell you that other people in your situation have had similar feelings and anxieties but we do not truly know what it is like for you and how it may affect your life. Many people have questions that, for the time being, cannot be answered fully because we are still studying the BRCA genes and their impact. One of the challenges that BRCA carriers face is coping with the uncertainty of what the future holds, both for you and your family. You may be asked to make life-changing decisions about cancer screening and risk-reducing surgery without the benefit of all the facts you would like. This may be difficult and could cause you to feel quite anxious, frustrated or even angry at times. It may take you some time to feel that you have absorbed enough information to feel confident about your decisions. Unlike other health-related issues there is an extra set of challenges for BRCA gene mutation carriers - the risks for your relatives. If you are the first person in the family to have been diagnosed with a BRCA gene mutation you will have to find a way to share this information with your family. Even if you aren t the first person in the family to be tested there may be family pressures to face. Will relationships be affected if one person has a positive gene test and their relative has a negative result? What about starting a new relationship when do you tell someone and what do you say? What if you have young children or are planning a family? We hope that this guide will be useful in providing you with some of the information you need and also help you to think about questions you may wish to discuss with your family and the genetics department. If you have any comments about the guide do let us know. We would like to make this booklet as useful and accessible as we can to support you and your relatives. 1

6 Background information about the BRCA1 and 2 genes Is breast cancer inherited? Generally speaking, cancer is not an inherited illness. Breast cancer is common, affecting about 1 in 8 women at some point during their life, more commonly after the menopause. It isn t unusual to have a relative who has been affected by breast cancer. Most breast cancer occurs sporadically or out of the blue. However, we know that faulty genes are the underlying cause for about 5 10% (5 to 10 in 100) of breast cancers. There are two genes that, if mutated, greatly increase an individual s chance of developing breast and ovarian cancer. These are known as BRCA1 (Breast Cancer 1) and BRCA2 (Breast Cancer 2) genes. These two genes account for approximately a fifth (20%) of familial breast cancers. Research to identify new genes that also contribute to a high risk of breast cancer or modify the risk associated with a BRCA1/2 mutation is ongoing. What are breast cancer genes? Genes are pieces of the DNA code that we inherit from our parents. We have two copies of each gene: one copy is inherited from our mother and one from our father. We have about 20,000 genes, each with a specific function that helps our bodies grow and function normally. Some genes work to protect against cancer by correcting damage that can occur in the DNA during cell division. BRCA1 and BRCA2 are two examples of these tumour suppressor genes. If an individual has a mutation in a BRCA1/2 gene they have a greatly increased risk of developing breast and ovarian cancer. The BRCA1/2 mutation does not cause cancer to occur on its own. The individual is at greater risk of developing cancer because their cells ability to repair DNA damage may be impaired by the BRCA1/2 mutation. It is the accumulation of DNA damage which causes a cell to change into a cancerous cell. We do not yet fully understand the whole process that changes a normal cell into a cancerous cell. We also do not yet understand why the BRCA1/2 mutations primarily give a high risk of breast, ovarian and prostate cancers, rather than other types of cancer. 2

7 A Beginner s Guide to BRCA1 and BRCA2 What are the cancer risks associated with BRCA1/2? Gene BRCA1 BRCA2 Breast cancer, in unaffected women (up to age 80) Women with breast cancer (unilateral) Lifetime risk of a new cancer in the other breast Ovarian cancer, lifetime risk Male breast cancer, lifetime risk 60 90% 45 85% 50% 50% 5 year risk of new breast cancer ~10% 40 60% Risk increases from age 40 5 year risk of new breast cancer ~ 5 10% 10 30% Risk increases from mid 40s 0.1 1% 5 10% Prostate cancer, lifetime risk ~10% Similar to population risk 20 25% Risk of developing breast cancer by age Current age BRCA1 BRCA2 Approximate remaining lifetime risk to 80 years Approximate 5 year risk Approximate remaining lifetime risk to 80 years Approximate 5 year risk % 5% 70% 1% % 5% 70% 2% % 5% 65% 5% % 10% 65% 5% % 10% 60% 10% % 15% 55% 10% % 15% 50% 10% % 10% 50% 10% % 10% 45% 15% % 10% 35% 15% 3

8 Screening Managing your risk of breast cancer Women who are carriers of a BRCA gene mutation have an increased risk of developing breast cancer during their lifetime. What is my risk compared with other women? Women in the UK have a 1 in 8 or 12.5% chance, on average, of developing breast cancer in their lifetime. Women with one or two close relatives affected with breast cancer have a lifetime risk of 17-30%, depending on the specific family history. Women who have a BRCA1 gene mutation have a 60-90% lifetime risk and women who have a BRCA2 gene mutation have a 45-85% lifetime risk. Women with BRCA mutations have an increased risk of developing breast cancer at a younger age. Also, BRCA mutation carriers who have had breast cancer have a higher risk of developing another new breast cancer, compared to women who develop sporadic breast cancer in the general population. How can I manage my risk of developing breast cancer? There are two approaches to managing your risk. You can choose to have cancer screening such as mammography to try to detect breast cancer at an early stage so it is possibly easier to treat. You can choose to have risk-reducing surgery to remove your breast tissue, before the diagnosis of breast cancer. Screening does not prevent or reduce the risk of breast cancer. Surgery has potential side effects that need careful consideration. Many women choose to have screening initially and some may also consider riskreducing surgery. Clinical trials are examining whether drugs can be given to try to prevent breast cancer in those who are at increased risk. This is known as chemoprevention. The National Institute for Clinical Excellence (NICE) is in the process of updating its guidance for the management of women at high risk of developing breast cancer. The new guidelines are due to be agreed and published in 2013 and may contain advice around chemoprevention. 4

9 A Beginner s Guide to BRCA1 and BRCA2 There is no right choice. Everyone has to decide which option is best for them. We can help you make that decision by ensuring you have accurate information and by referring you to speak to the appropriate specialists. What breast cancer screening is recommended for BRCA mutation carriers? Breast awareness: This involves being aware of changes in the breast and feeling the breast with the flat of the hand in a systematic way once a month 5-10 days after you have finished your period. It is also important to take time to look at your breasts in different positions. If there are any changes at all you should inform your doctor. All women should practice this from their early 20s. Breast screening: Mammography is offered annually from age Magnetic resonance imaging: MRI is a new form of breast screening that is being introduced for young women at increased risk of breast cancer. It is a more sensitive screening technique, compared with mammography in women under 50. It is currently recommended that women, who are known carriers of either BRCA1 or BRCA2 mutations, aged have annual MRI screening. If I have breast cancer what is the chance that it will be detected on a mammogram? Mammography has been shown to be effective in detecting breast cancer in women over 50. If a woman over 50 has breast cancer there is about 85% chance that mammography will detect it. This is called the sensitivity of the test. There is less evidence available about the sensitivity of mammography in women under 50. For example, in some studies of women aged the sensitivity of mammography ranged from 62-76%. The sensitivity of mammography in young BRCA carriers (aged 35-49) has been demonstrated to be around 40%. This difference in sensitivity is one of the reasons we suggest that women have annual mammography rather than every two or three years. 5

10 If I have breast cancer what is the chance that it will be detected on a MRI scan? Studies on young women (aged 35-49) who carry BRCA mutations have demonstrated that MRI screening is more effective at detecting breast cancer than mammography (77% versus 40%). Also, studies showed that combining both MRI and mammography screening improves the detection rate for both BRCA1 and BRCA2 mutation carriers to 94%. One drawback of MRI screening is that there is a higher recall rate to investigate abnormalities that may not be cancer, compared with mammography. Further research is ongoing into the usefulness of MRI screening for BRCA mutation carriers. What does it mean if I am called back for another scan? If something unusual is found on your mammogram or MRI scan you will be recalled for further examinations to clarify what the abnormality is. It is not unusual to be recalled following your first mammogram or MRI. After your first screening examination the doctors will have images to compare, making it easier to tell if further investigations are needed. You may be recalled because of suspicious results or technical issues. If you are recalled you may have a clinical exam, a mammogram taking views from different angles, an ultrasound scan and, if needed, a biopsy to determine the nature of the abnormality. Not everyone who is recalled will be diagnosed with breast cancer but the extra investigations can be uncomfortable and it can be a stressful time waiting for the results. This is why it is important that a screening test is good at detecting cancer when it is present and has a low recall rate. Why can t I have the ultrasound scans to screen for breast cancer? Studies have shown that an ultrasound scan is not an effective tool for routine screening for breast cancer. Ultrasound examinations are used to clarify the finding of a clinical breast examination, mammogram or MRI scan, where a lump or thickened area has been detected. It is also used when biopsies are taken. 6

11 A Beginner s Guide to BRCA1 and BRCA2 What choices can you make to help to reduce your risk of developing breast cancer? Risk-reducing surgery: Women who have risk-reducing mastectomies reduce their risk of developing breast cancer to less than 5% over their lifetime, which is less than the risk in the general population. Women who have their ovaries removed before the menopause reduce their risk of developing breast cancer by up to 50%, even when hormone replacement therapy is given. Lifestyle and diet: Currently there is no definitive scientific evidence to suggest that there are specific lifestyle or dietary factors that reduce or increase the risk of breast cancer for BRCA carriers. Many scientific studies in the general population have shown that limiting alcohol consumption, maintaining a healthy weight, being physically active, and breast feeding can help women to reduce their overall risk of developing breast cancer. Having a healthy diet that includes plenty of fruit and vegetables, pulses and whole grain foods can help you maintain a healthy weight. The Pill: There may be a small increase in breast cancer risk if the oral contraceptive pill is used for more than four years but evidence is still being gathered on this. It is not known if the minipill is a safer than the combined pill but it is one alternative that women may consider. Another alternative is the Mirena coil. We advise that women discuss their contraception with their GP to assess the range of options. HRT: Studies have shown that women who take hormone replacement therapy (HRT) after the natural menopause (especially the combined HRT, rather than oestrogen only HRT) have a slightly increased risk of developing breast cancer compared with women who do not take HRT. However once women stop taking HRT their risk goes back to normal within 5 years of stopping HRT. We do not know if this same effect occurs in BRCA mutation carriers. However women who have risk-reducing surgical removal of their ovaries (bilateral salpingo-oophorectomy) at a younger age are usually offered HRT to prevent significant menopausal symptoms. Evidence indicates that these women still have reduction in breast cancer risk (despite taking HRT) if their ovarian surgery is undertaken before age 50. 7

12 Managing your risk of ovarian cancer Women who are carriers of a faulty BRCA gene have an increased risk of developing ovarian cancer during their lifetime. What is my risk compared with other women? On average women have about a 2% chance of developing ovarian cancer in their lifetime. Women with a close relative affected with ovarian cancer may have a slightly increased risk of around 4-5%. Women who have a faulty BRCA1 gene have a 40-60% lifetime risk of developing ovarian cancer. Women who have a faulty BRCA2 gene have a 10-30% lifetime risk of developing ovarian cancer. The risk of developing ovarian cancer starts to increase from around the age of 40 for BRCA1 carriers and in the mid 40s for BRCA2 carriers. What are the symptoms of ovarian cancer? It is important to be aware of ovarian cancer symptoms and discuss them with your GP. Ovarian cancer was once known as a silent disease, because its symptoms can be vague. Evidence now shows that any of the following three symptoms, if they occur on most days may suggest ovarian cancer: persistent pelvic and abdominal pain increased abdominal size or persistent bloating (not bloating that comes and goes) difficulty eating, and feeling full quickly Occasionally, women may also experience other symptoms, such as urinary symptoms, changes in bowel habit, extreme fatigue or back pain, on their own or at the same time as those listed above. These symptoms are unlikely to be ovarian cancer, but may be present in some women with the disease. If you regularly experience any of these symptoms and they re not normal for you, see your GP. There is a further leaflet available on: 8

13 A Beginner s Guide to BRCA1 and BRCA2 Is ovarian cancer screening available? Currently there is no proven test or group of tests that reliably diagnoses ovarian cancer at an early stage. Therefore no routine screening for ovarian cancer is currently available. Is there any research into ovarian screening? A large study called the UK Familial Ovarian Cancer Screening Study (UKFOCSS) recruited patients from to look at how to screen high risk women for ovarian cancer. They expect to report their findings about the effectiveness of their screening technique in 2013/14. It takes a long time to study a new screening technique in order to get meaningful results. How did the UKFOCSS screen women for ovarian cancer? Women aged 35 and over were recruited to this study. They were offered annual ovarian ultrasound examinations and blood tests to measure a protein called CA125 three times a year. The ultrasound aims to detect changes in the size and appearance of the ovaries. The CA125 protein level is often raised in women who have ovarian cancer. The study was trying to see if small increases in the CA125 level were an indicator of early signs of ovarian cancer and to determine how often the CA125 would have to be measured, in order to detect ovarian cancer at an early stage. Have there been any results from the study yet? The early results from the study indicate that if a woman has normal CA125 levels and a normal scan it is unlikely that she has ovarian cancer at the time the tests are done. However, women on the study who were diagnosed with ovarian cancer were not all detected at an early stage of the disease. Further research and analysis is needed before we know if ovarian screening is effective in improving survival from ovarian cancer. 9

14 Why can t I have the ultrasound and blood test anyway? The problem with having these tests without knowing if they actually work as a screening test is the risk of a false positive result women may get results which initially appear abnormal and need further, possibly invasive testing to clarify the results. This can be very stressful for women even when they get a normal result at the end of their investigations. The other problem is that this test may be falsely reassuring and women may discount the option of risk-reducing surgery if they are having these tests. We can only offer a screening test if it has a good rate of detecting cancers at an early stage and a low false positive rate meaning that it doesn t identify too many women incorrectly as having signs of ovarian cancer. What is available then? We know that taking the oral contraceptive pill is protective against developing ovarian cancer. However, if women with BRCA mutations take the pill for an extended period of time (more than four years), it may slightly raise their risk of developing breast cancer. The other option women can consider is having risk-reducing surgery to remove their ovaries and fallopian tubes, before any cancer is diagnosed. 10

15 A Beginner s Guide to BRCA1 and BRCA2 Reducing risk Risk-reducing mastectomy Women who have a faulty BRCA1 or BRCA2 gene may choose to have screening to manage their increased risk of breast cancer. However the main drawback to screening is that it does not prevent cancer. If a woman wishes to reduce her risk of developing breast cancer she could consider risk-reducing mastectomies. This is the surgical removal of breast tissue to try to prevent the development of cancer. There are various types of operations, but, in general, as much breast tissue as possible is removed. There will be some breast tissue remaining but the lifetime risk of breast cancer would generally be reduced by 90-95%. Women who have the risk-reducing surgery will no longer need annual mammographic screening because they will have very little breast tissue left. Reconstructive surgery can be offered at the same time as the risk-reducing mastectomies. Making a decision to have risk-reducing surgery is very personal and very complex. There are many factors to consider. There are decisions to be made about the type of surgery you wish to have. The surgical team will explain the options to you over several appointments. You will have a chance to look at pictures with the breast nurse and speak with a clinical psychologist about the potential emotional impact of the surgery. One advantage of having risk-reducing surgery is that you can pick a time to have surgery and make arrangements in advance regarding work and childcare for your recovery period. A booklet called Understanding Risk-reducing Breast Surgery Prophylactic Mastectomy and Reconstruction produced by Macmillan Cancer Support provides information about many aspects of this surgery, for women who are considering this option. The booklet includes information about the surgery, reconstruction techniques, recovery, possible complications, the emotional effects of having the surgery and sources of additional information. If you are interested in finding out more about having risk-reducing surgery you can ask for a referral to the breast team. You would be under no obligation to go ahead with the surgery. We recognise as much information as possible is needed before this type of decision is made. 11

16 Breast surgery options for women affected with breast cancer For BRCA carriers, the risk of cancer recurring in the affected breast is not significantly increased compared to other women with the same type of breast cancer, but the risk of developing a new tumour in the other (unaffected) breast is greater. This risk is about 50% if women are followed up to age 80. Having both breasts removed (bilateral mastectomy with reconstruction) will reduce this long-term risk to less than 5%. It will avoid the need for future breast screening by mammograms and MRI (magnetic resonance imaging). This surgery minimises the likelihood of needing treatment for a new cancer in either breast. It may provide an improved sense of control over risk and may avoid the worry associated with having breast imaging. We do not know, however, that mastectomies are necessary to maximise a woman s survival chances. This is because many factors may influence an individual s long term survival such as treatment including chemotherapy and other follow-up such as breast imaging which aims to find new cancers (if they occur) as early as possible. Some BRCA carriers (or other women at high risk) feel that mastectomies (usually with reconstruction) are not for them. They prefer to have lumpectomy, radiotherapy and then breast screening. There are a number of factors to consider in making such a surgical choice. These include how a woman feels about the impact of surgery on her body image and relationships. The decision-making involves discussions with different health professionals to help a woman decide what choice is best for her. Some women may choose to have lumpectomy and radiation as their initial treatment and to think about further surgery later to both breasts. This is an option, although the skin elasticity after radiation can be less which can affect the type of reconstructive choices available. 12

17 A Beginner s Guide to BRCA1 and BRCA2 Risk-reducing ovarian surgery and surgical menopause What is a risk-reducing bilateral salpingo-oophorectomy (BSO)? A risk-reducing bilateral salpingo-oophorectomy (BSO, Bilateral (both sides) salpingo- (fallopian tube), oophor- (ovaries), ectomy (excision of)) is the surgical removal of a woman s ovaries and fallopian tubes before an ovarian cancer has occurred. This surgery is carried out to reduce the risk of developing ovarian or fallopian tube cancer. How do the ovaries normally work? Normally a woman has two ovaries and each month an egg is released from one of the ovaries. If the egg is fertilised a pregnancy may result. If a pregnancy does not occur, the lining of the womb (uterus) falls away and the women has her period. As well as storing and producing eggs, ovaries produce the female sex hormones called oestrogen and progesterone. These hormones cause a woman s breasts to develop, help make periods regular and work to build up the lining of the womb each month 13

18 to support a pregnancy (if it occurs). The ovaries also produce a hormone called testosterone that influences hair growth and sex drive (libido). As a woman ages and gets closer to the menopause, the ovaries make less of these hormones and her periods gradually stop. For most women this usually happens between the early-40s and mid-50s. Who is offered a risk-reducing BSO? Some women, for example BRCA mutation carriers, are advised to consider risk-reducing BSO because they have a high risk of developing cancer of the ovaries. In this situation it is also recommended that the fallopian tubes be removed at the same time, as this tissue is similar to that of the ovaries. Women may choose to have risk-reducing BSO after they have considered their individual risk of ovarian cancer against the risks of the surgery, the risk of premature menopause and depending on personal circumstances, such as their family planning situation. What is the risk of ovarian cancer for BRCA carriers? Women who have a BRCA1 mutation have a lifetime risk of 40-60% of developing ovarian cancer. Their risk of ovarian cancer starts to increase in the early-40s. Women who have a BRCA2 mutation have a lifetime risk of 10-30% of developing ovarian cancer. Their risk of ovarian cancer starts to increase in the mid-40s. Are there other risk management options available? Screening Unlike surgery, screening does not reduce the risk of developing ovarian cancer. The aim of screening is to detect ovarian cancer at an early stage. Currently in the UK ovarian screening is not offered to women through the NHS because we do not know if it is effective. A large study was carried out to evaluate whether screening is useful in detecting ovarian cancer. This study was called The UK Familial Ovarian Cancer Screening Study (UKFOCSS). The results of this study will help to determine whether screening should be offered as a clinical service. 14

19 A Beginner s Guide to BRCA1 and BRCA2 The oral contraceptive pill The oral contraceptive pill has been shown to reduce the risk of ovarian cancer by a factor of about a half when taken for several years. However, the oral contraceptive pill is also known to increase the risk of breast cancer slightly if taken for more than four years. The benefits and risks of taking the pill as a riskreducing option should be carefully discussed with your doctors. The most effective way to minimise ovarian cancer risk is still a risk-reducing BSO as this reduces the risk to less than 5%. What if I prefer not to choose any of these options? After discussion with your doctor you may decide that none of these options are appropriate for you at this time. It may be that you are younger than the recommended age for surgery, or it may be that you wish to stay fertile as you have not completed your family. It is important to make the decision that is right for you and this decision can be discussed with your doctor, nurse or genetic counsellor at any time. For women who choose not to have surgery there are certain advantages and disadvantages that need to be considered. The advantages include that you will remain fertile (if you have not yet gone through the menopause) and that there are no side-effects (see complications of surgery below). The disadvantage of not having surgery is that it is not easy to recognise the signs and symptoms of ovarian cancer during the early stages. If ovarian cancer does occur and is only found at an advanced stage, it is much more difficult to treat effectively. When should I consider having risk-reducing surgery? The age at which a woman s risk of developing ovarian cancer becomes significant will vary depending on her family history and which gene fault is present. The risk of ovarian cancer in women who carry a BRCA1 or BRCA2 gene fault does not begin to rise markedly until about the age of 40 for BRCA1 carriers and in the mid-40s for BRCA2 carriers. Risk-reducing BSO is generally performed in women in their early to mid-40s. 15

20 For most women, the value of risk-reducing BSO before the age of 40 is minimal. However, a very small group of women, who have a strong family history of cancer of the ovaries before the age of 40, can be offered risk-reducing BSO earlier. How is risk-reducing BSO performed? There are two main surgical ways of removing the ovaries; keyhole (laparoscopy) or open surgery (laparotomy). Both are carried out under general anaesthetic. Whichever approach is used, after the operation both ovaries and tubes will be sent to a laboratory to check if ovarian cancer is already present. You will get an outpatient appointment about four weeks after the procedure to discuss the final pathology results. Laparoscopy or keyhole surgery: Most risk-reducing BSOs are done using this method. A small 1cm cut (incision) will be made in the belly button (umbilicus) through which a camera will be inserted. Carbon dioxide gas is used to inflate the abdomen so that the surgeon will be able to see the pelvic organs. The laparoscope relays pictures to a television screen and the surgeon is able to view the internal organs and abdomen. These images give the surgeon an external view of the pelvis from where they can carry out this procedure. A further two or three small incisions will then be made in the lower abdominal wall to create space for the safe insertion of instruments with which the surgeon will remove the ovaries and tubes. While this is a standard procedure used by gynaecological surgeons it should be noted that different surgeons use slightly different techniques. Some women feel some discomfort after surgery, mainly shoulder pain or bloating related to the use of the carbon dioxide gas. As with all operations, it is normal to feel tired for a day or two after the surgery. Laparotomy or open surgery: This procedure involves the removal of the ovaries by a larger cut in the lower abdomen, usually along the bikini line. One in 20 women who opt for keyhole surgery have an open incision performed instead as it may not be possible to perform the procedure with the laparoscope. Women who are more likely to need an open 16

21 A Beginner s Guide to BRCA1 and BRCA2 incision include those who are overweight, those in poor general health, who have had previous operations on their abdomen, who have had a hysterectomy, women with a disease known as endometriosis and women with a condition known as pelvic inflammatory disease. How do the two methods compare? Keyhole surgery usually involves one overnight stay in hospital. Some keyhole surgery may be carried out as a day case, if this is considered appropriate for the patient. The average hospital stay for open surgery (when keyhole surgery is not considered the appropriate procedure for the patient) is increased to about five nights. The average return to normal activity is two to three weeks for keyhole surgery compared with about four to six weeks for open surgery. These figures are averages and this does vary a lot between different people depending on their usual work, family and exercise commitments. Both procedures take about the same operating time. Patients often ask when they can travel after surgery, in particular travel by plane. This does need to be discussed before the procedure due to the variations in patients age, general health, post-operative recovery and their lifestyle commitments. What other procedures are carried out? The womb is not usually removed as part of the risk-reducing BSO operation, although some women with a history of gynaecological problems may consider having a hysterectomy (removal of the womb) during the surgery. A hysterectomy is a bigger operation and may lengthen the hospital stay and time spent getting better. Some gynaecologists prefer to obtain a sample of lining from the womb (endometrium) during the procedure, known as curettage. Before the procedure it is common practice to carry out a transvaginal ultrasound scan to assess the womb and ovaries and a blood test to check the levels of an ovarian tumour marker called CA125. If the surgery is delayed following these investigations, for whatever reason, the gynaecologist may wish to repeat both investigations before the new surgery date. 17

22 Who should carry out the operation? The operation is not carried out by one person but by a team. A consultant gynaecology surgeon is usually head of that team. In the UK, that consultant would usually be a member or a fellow of the Royal College of Obstetricians and Gynaecologists (RCOG) and be on the specialist register of the General Medical Council (GMC). In addition, the RCOG issue certificates to surgeons who demonstrate that they have trained in laparoscopic surgery. What are the complications of risk-reducing BSO? There are complications associated with of any type of surgery. The main possible complications are infection of the bladder, wound or urine, bleeding at the time of surgery requiring a blood transfusion, or the formation of blood clots. There is also a risk of herniation from the small abdominal incisions (so-called port sites) and damage to surrounding organs like viscera, bowel or bladder resulting in laparotomy (open procedure) to repair them. Fortunately these complications are relatively rare. Women at greater risk of complications include those with other illnesses, those who are overweight, those who smoke and those who have had previous surgery. You should discuss your own individual risk with your surgeon. What are the advantages of risk-reducing BSO? Risk-reducing BSO minimises the lifetime risk of ovarian cancer to less than 5% in some studies. If a woman with a BRCA1 or BRCA2 alteration has a riskreducing BSO performed before they reach the menopause then studies have shown that they may also reduce their risk of breast cancer by half. What are the disadvantages of risk-reducing BSO? While risk-reducing BSO minimises the risk of ovarian cancer, it cannot reduce the risk by 100%. On very rare occasions it is not possible to remove all ovarian tissues due to scar tissue (adhesions). Another rare situation is that women may develop cancer of the lining of the abdominal wall (peritoneum). This type of cancer is clinically identical to ovarian cancer. 18

23 A Beginner s Guide to BRCA1 and BRCA2 Once the ovaries are removed, a woman is no longer fertile and is unable to have children naturally. Women choosing to have risk-reducing BSO before the menopause may experience the symptoms of a surgical menopause, which is described below. Some may have no significant symptoms at all; it varies greatly from person to person. Surgical menopause The most significant side-effect of BSO is the experience of going through the menopause. The menopause is the time in a woman s life when she stops having periods. While this usually only affects women who have not yet gone through the menopause, some women who are going through the menopause may find their symptoms get worse after the surgery. The natural menopause is usually very gradual, giving a woman time to adjust to the changes that are happening to her body. However, when the menopause occurs because the ovaries are surgically removed the symptoms can be quite severe and women may have a delay before receiving HRT while waiting for pathology results. What is the menopause? According to the British Menopause Society, the menopause is the permanent cessation of periods that results from the loss of ovarian activity. The ovaries stop producing an egg every month and the woman stops menstruating. The average age of menopause in the UK is 52. Menopause before the age of 45 is known as early or premature menopause. The process is usually gradual, as the ovaries slowly stop producing hormones, but if the ovaries are surgically removed then menopause will be immediate. 19

24 Menopausal symptoms: Not all women experience the same type or severity of symptoms. Some of the issues reported by women are listed below. It is important to remember that only a minority of women have very severe symptoms or many symptoms at at the same time. Hot flushes and accompanying sweats, often at night (75% of women experience this, more so in the first two years, but 20-50% continue long term) Headaches, lack of concentration/memory, low mood, insomnia Uncharacteristic tiredness, anxiety and irritability Palpitations, panic attacks Loss of bone mass or pain in joints Vaginal dryness/itching, reduced sex drive Dry skin, brittle hair, thinner hair, weight gain Stress and urge incontinence, urinary tract infections How will menopause affect me? It is difficult to predict how menopause will affect you as an individual. Menopausal symptoms do not run in the family, although the age of menopause can. Women experience menopause very differently, even within the same family. Treatment will be individualised and based on personal symptoms. How does menopause affect bone health? It is normal to lose bone density as women get older. Oestrogen works to ensure that calcium is not lost and protects against thinning of the bones. Osteoporosis is when the bones become weak and more likely to break. Often there are no signs of osteoporosis and it is only found after someone has a fracture, maybe after a fall. There are several risk factors for osteoporosis, including family history, low body weight, diet/nutritional deficiencies, smoking, some medications like corticosteroids, and premature menopause. If you have your ovaries removed 20

25 A Beginner s Guide to BRCA1 and BRCA2 before 50, you should have your GP organise a bone density test (DEXA scan) at the time of surgery (baseline) and then every three to five years. If the bone density is low, the test should be repeated two-yearly. Treatment for low bone density can include a recommendation to eat healthily, take regular weight-bearing exercise and sometimes medication. How does menopause affect heart health? Oestrogen helps to control the level of cholesterol and other fats in the blood. After the menopause, the drop in oestrogen levels means fats could build up in the blood vessels of the heart, contributing to the development of coronary heart disease. Lifestyle advice and medication may be given to control the level of cholesterol and fats in the blood. What is Hormone Replacement Therapy (HRT)? Hormone Replacement Therapy (HRT) replaces the hormones such as oestrogen and progesterone that are lost when a woman has her ovaries removed. HRT comes in many preparations, some containing both oestrogen and progesterone (combined HRT) and some contain oestrogen alone (for women who have had a hysterectomy). Should I take Hormone Replacement Therapy? If you have your ovaries removed before age 50 and you have never had breast cancer, HRT is likely to be recommended for you. Studies have shown that HRT is safe in BRCA mutation carriers who have an early menopause after surgery. You might have to wait several weeks before starting the HRT while the tissue from your operation is checked for any signs of cancer. If you are near to the age of 50 then you might decide with your doctor to wait and see how your symptoms are and consider treatment options. If you have had breast cancer that was hormone (oestrogen/progesterone receptor) positive, you might be taking hormone therapy such as tamoxifen. Your oncologist will probably suggest that you do not take HRT, although if there are significant symptoms affecting your quality of life then discussion should be held with your treating team. 21

26 Does HRT increase breast cancer risk? Some members of the public and health care professions still associate HRT with negative outcomes. It is important to distinguish between women taking HRT for many years after the natural menopause from young women taking HRT because they had early menopause (including spontaneous/medically or surgically induced). Having your ovaries removed before age 50 is known to protect against breast cancer. It is important to remember that the level of hormones in the HRT will be much less than the ovaries would have been making naturally if a woman still had her ovaries. Studies show that risk-reducing BSO before the age of 50 overall decreases the risk of breast cancer in high-risk women even when they take HRT. HRT is safe and recommended in young women to help offset the risk of other potential health problems. What other options are available and how should I choose? This should be done in consultation with a health care professional. You might need to try different options before finding the right treatment for you. If women are having significant menopause symptoms they can be referred to a specialist menopause clinic for advice. There are many different preparations of HRT and several nonhormonal treatment options. Selecting the most appropriate solution may be an ongoing process, depending on your symptoms and how you react to treatment. Aerobic exercise can improve quality of life and psychological health in women with hot flushes as well as help with low mood and insomnia. Infrequent high impact exercise can actually make symptoms worse, and it appears preferable to have regular, sustained activity (such as swimming or running). Occasionally women can feel tired and depressed as a result of low testosterone; so-called female androgen deficiency syndrome and this can be treated with testosterone replacement therapy. Venlaxifine is an anti-depressant that can help with low libido; this should only be considered after careful discussion with your doctor. Avoiding or 22

27 A Beginner s Guide to BRCA1 and BRCA2 reducing alcohol or caffeine can help with hot flushes and sweats. Yoga and relaxation techniques such as massage or reflexology help some women to manage stress. If vaginal dryness is a problem, lubricants could be helpful. The options for treating symptoms are normally addressed postoperatively once pathology results are available as it is impossible to know what symptoms each woman will experience after her surgery. Advice can be provided by your gynaecologist, your CNS, your GP or through a specialist menopause clinic. Where can I get more information about menopause? The Menopause Matters website has information, a magazine, an online forum and links to other sources of information: Where else can I find information concerning risk-reducing BSO? The decision to undergo risk-reducing BSO can be a difficult one to make. There are many advantages and possible disadvantages to be weighed up including the effects on body image and lifestyle. It is important that the decision you make is the right one for you and that you have access to all the information you need to make the decision about whether to have surgery. This leaflet has covered most aspects of risk-reducing BSO. More detailed information is normally specific to individuals and best discussed with your surgeon, genetics doctor or genetic counsellor, oncologist, your family doctor or clinical nurse specialist. 23

28 Sharing information with your family General issues Who needs to know that a BRCA gene mutation has been identified? During your genetic counselling session the doctor or the genetic counsellor will go through your family tree with you to identify who is at risk of inheriting the faulty BRCA gene. Cancer susceptibility due to a faulty BRCA1 or BRCA2 gene is inherited. Your close relatives (brothers, sisters and your children) will have a 50% chance of inheriting the faulty BRCA gene. In most families it will be easy to predict if the faulty BRCA gene came down through your mother s or your father s family because of the family history of cancer. The only way to prove this is to test family members to see who has the faulty gene. Only your relatives from that side of the family will have a risk of inheriting the faulty BRCA gene. What do I tell people? You will have received quite a lot of information about the BRCA gene, your risks and your options. It can be a bit daunting to know how to share all this information with someone else. Many people worry that they will be asked questions and they won t know the answers. Your genetics unit will not approach your relatives about your result, so usually it is you who would provide this initial information about the presence of a faulty BRCA gene to the family. The geneticists can provide you with a To Whom it May Concern letter for you to share with your relative(s) which contains all the required information so that they can ask for a referral from their GP to their local genetics unit. Why do other people in my family need this information? Genetic information is different from most medical information an individual receives, because it is not only relevant to the individual but also to their family members. Genetic information can provide an explanation as to why someone has a particular health problem, but it can also predict future poor health or the risk of having a child affected with a particular genetic problem. If 24

29 A Beginner s Guide to BRCA1 and BRCA2 someone is aware that they have an increased risk of developing cancer, they have the chance to make choices about genetic testing, cancer surveillance or preventative surgery. They may also decide to make changes to their lifestyle to help decrease their risk of developing cancer, and they may wish to consider the family planning implications and insurance issues. Knowing about the risk gives your relatives a chance to take action to reduce their risk of getting cancer or help ensure that cancer is detected at an early stage so it can be treated more effectively. When should I share this information? There is probably no right time to tell people. Sometimes families are aware of the testing process and are waiting to hear the results. Other people choose to wait until they know their results before they mention it to anyone else. There will be a variety of factors that affect your decision to share this news, for example you may need time to get used to the information first, or someone may have been bereaved recently and you may feel it is better to wait a bit. Sometimes people are too young to be told everything or maybe you are waiting until you have the chance to see someone in person rather than telling them over the telephone or by mail. Women can start breast screening from 30 years of age so if your female relative is over 30 she could start breast cancer screening right away if she is at risk of having the faulty BRCA gene. Anyone in the family who has been affected with breast, prostate or ovarian cancer should be told as soon as possible because their doctors may need this information to make appropriate treatment decisions. It is important to highlight that women who are closely related (sister, daughter) to a person with a faulty BRCA gene can also have cancer screening, without undergoing genetic testing. We realise that not everyone wishes to have the genetic test. How can I avoid upsetting my relative? Many people are concerned that sharing this information will cause their relative to feel very anxious or guilty and responsible for causing this upset. It is always difficult to share bad news. It might be useful to think of other times that you have had to share bad news, how you did it and what you learned from that 25

30 experience. It may be useful if you think about this information in a positive light; that members of your family, with this information, are in a better position to make choices that could reduce their risk of cancer or ensure it is detected as early as possible. It is important to remember that if someone has this BRCA gene mutation it is nobody s fault we cannot control which genes were passed on to our children. It is also important to remember that if someone has a faulty BRCA gene they have always had it since the moment they were conceived, so what is different now is that we can identify it and give people options to manage their risk. Where can I get help with telling my family? The genetics team can help you to identify who needs to be informed in your family and provide you with a To Whom It May Concern letter. We can provide you with a copy of a letter that was written by a lady with BRCA gene mutation to her family, which is an example of how someone else in your situation chose to share information. There is a resource list which can direct you and your family to additional sources of information. It can be a burden to have this responsibility. Perhaps there is someone else within your family that you could share the information with and who could then help by taking on some of the responsibility of telling other people within the family. In some families we see the information being passed on to one generation and it is then passed down within family units. The genetics team can discuss strategies for sharing information with you to make it as easy as possible. Who is at risk of having the faulty BRCA gene in my family? If you are a BRCA mutation carrier, your close relatives have a 50/50 risk of having the faulty BRCA gene. The faulty gene would have been present in your family for many generations; it is not new within your family. It is only that we are now able to identify who actually carries the faulty gene. You would have inherited the BRCA mutation from either your mother or your father. This faulty BRCA gene causes the increased risk of developing cancer. 26